ribociclib 在黑人转移性乳腺癌患者中的药代动力学和药物基因组学 LEANORA 研究。
Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study.
发表日期：2024 Sep 30
作者：
Ilana Schlam, D Max Smith, Cody Peer, Tristan Sissung, Keith T Schmidt, Ming Tan, Ami Chitalia, Nanette H Bishopric, Seth Steinberg, Hyoyoung Choo-Wosoba, Giulia Napoli, Christopher Gallagher, Nadia Ashai, Kristen Whitaker, Candace Mainor, Shruti Tiwari, Nicole Swanson, Stacy Malloy, Claudine Isaacs, William Douglas Figg, Sandra M Swain
来源：
npj Breast Cancer
摘要：
代表性不足的人群对临床试验的参与仍然有限，基因组变异对药物代谢的潜在影响仍然难以捉摸。本研究旨在评估 ribociclib 在自认患有激素受体阳性 (HR )/人表皮生长因子受体 2 阴性 (HER2) 晚期乳腺癌的黑人女性中的药代动力学 (PK) 和药物基因组学 (PGx)。 LEANORA (NCT04657679) 是一项前瞻性、观察性、多中心队列研究，涉及 14 名黑人女性。使用串联质谱和 PharmacoScan™ 微阵列（包括 CYP3A5*3、*6 和 *7）评估 PK 和 PGx。参与者之间的 CYP3A5 表型各不相同：7 名代谢不良者 (PM)、6 名中间代谢者 (IM) 和 1 名正常代谢者 (NM)。 PM (39,230 h*ng/mL) 和 IM/NMs (43,546 h*ng/mL；p = 0.38) 之间的曲线下面积没有显着差异。不良事件（AE）的发生率也相似。我们发现 CYP3A5 基因型与 ribociclib 暴露之间没有关联。需要继续努力将不同人群纳入临床试验，以确保公平的治疗结果。© 2024。作者。
Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan™ microarray (including CYP3A5*3, *6, and *7). CYP3A5 phenotypes varied among participants: 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area under the curve did not significantly differ between PMs (39,230 h*ng/mL) and IM/NMs (43,546 h*ng/mL; p = 0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.© 2024. The Author(s).